Mechanics of diffusion-mediated budding and implications for virus replication and infection

Budding allows virus replication and macromolecular secretion in cells. It involves the formation of a bud, i.e. an outgrowth from the cell membrane that evolves into an envelope. The largest energetic barrier to bud formation is membrane deflection and is trespassed primarily thanks to nucleocapsid-membrane adhesion. Transmembrane proteins (TPs), which later form the virus ligands, are the main promotors of adhesion and can accommodate membrane bending thanks to an induced spontaneous curvature. Adhesive TPs must diffuse across the membrane from remote regions to gather on the bud surface, thus, diffusivity controls the kinetics. This paper proposes a simple model to describe diffusion-mediated budding unraveling important size limitations and size-dependent kinetics. The predicted optimal virion radius, giving the fastest budding, is validated against experiments for Coronavirus, HIV, Flu, and Hepatitis. Assuming exponential replication of virions and hereditary size, the model can predict the size distribution of a virus population. This is verified against experiments for SARS-CoV-2. All the above comparisons rely on the premise that budding poses the tightest size constraint. This is true in most cases, as demonstrated in this paper, where the proposed model is extended to describe virus infection via receptor- and clathrin-mediated endocytosis, and via membrane fusion

Multi-material topology optimization of adhesive backing layers via J-integral and strain energy minimizations

Strong adhesives rely on reduced stress concentrations, often obtained via specific geometry or composition of materials. In many examples in nature and engineering prototypes, the adhesive performance relies on structural rigidity being placed in specific locations. A few design principles have been formulated, based on parametric optimization, while a general design tool is still missing. We propose to use topology optimization to achieve optimal stiffness distribution in a multi-material adhesive backing layer, reducing stress concentration at specified locations. The method involves the minimization of a linear combination of J-integral and strain energy. While the J-integral minimization is aimed at reducing stress concentration, we observe that the combination of these two objectives ultimately provides the best results. We analyze three cases in plane strain conditions, namely (i) double-edged crack and (ii) center crack in tension and (iii) edge crack under shear. Each case evidences a different optimal topology with (i) and (ii) providing similar results. The optimal topology allocates stiffness in regions that are far away from the crack tip, intuitively, but the allocation of softer materials over stiffer ones can be non-trivial. To test our solutions, we plot the contact stress distribution across the interface. In all observed cases, we eliminate the stress singularity at the crack tip. Stress concentrations might arise in locations far away from the crack tip, but the final results are independent of crack size. Our method ultimately provides optimal, flaw tolerant, adhesives where the crack location is known

Making the cut: end effects and the benefits of slicing

Cutting mechanics in soft solids have been a subject of study for several decades, an interest fuelled by the multitude of its applications, including material testing, manufacturing, and biomedical technology. Wire cutting is the simplest model system to analyze the cutting resistance of a soft material. However, even for this simple system, the complex failure mechanisms that underpin cutting are still not completely understood. Several models that connect the critical cutting force to the radius of the wire and the key mechanical properties of the cut material have been proposed. An almost ubiquitous simplifying assumption is a state of plane (and anti-plane) strain in the material. In this paper, we show that this assumption can lead to erroneous conclusions because even such a simple cutting problem is essentially three-dimensional. A planar approximation restricts the analysis to the stress distribution in the mid-plane. However, through finite element modeling, we reveal that the maximal tensile stress - and thus the likely location of cut initiation - is in fact located in the front plane. Friction reduces the magnitude of this stress, but this detrimental effect can be counteracted by large slice-to-push (shear-to-indentation) ratios. The introduction of these end effects helps reconcile a recent controversy around the role of friction in wire cutting, for it implies that slicing can indeed reduce required cutting forces, but only if the slice-push ratio and the friction coefficient are sufficiently large. Material strain-stiffening reduces the critical indentation depth required to initiate the cut further and thus needs to be considered when cutting non-linearly elastic materials

Theoretical Puncture Mechanics of Soft Compressible Solids

Accurate prediction of the force required to puncture a soft material is critical in many fields like medical technology, food processing, and manufacturing. However, such a prediction strongly depends on our understanding of the complex nonlinear behavior of the material subject to deep indentation and complex failure mechanisms. Only recently we developed theories capable of correlating puncture force with material properties and needle geometry. However, such models are based on simplifications that seldom limit their applicability to real cases. One common assumption is the incompressibility of the cut material, albeit no material is truly incompressible. In this paper we propose a simple model that accounts for linearly elastic compressibility, and its interplay with toughness, stiffness, and elastic strain-stiffening. Confirming previous theories and experiments, materials having high-toughness and low-modulus exhibit the highest puncture resistance at a given needle radius. Surprisingly, in these conditions, we observe that incompressible materials exhibit the lowest puncture resistance, where volumetric compressibility can create an additional (strain) energy barrier to puncture. Our model provides a valuable tool to assess the puncture resistance of soft compressible materials and suggests new design strategies for sharp needles and puncture-resistant materials

Energetics of Cytoskeletal Gel Contraction

Cytoskeletal gels are prototyped to reproduce the mechanical contraction of the cytoskeleton in-vitro. They are composed of a polymer network (backbone), swollen by the presence of a liquid solvent, and active molecules (molecular motors, MMs) that transduce chemical energy into the mechanical work of contraction. These motors attach to the polymer chains to shorten them and/or act as dynamic crosslinks, thereby constraining the thermal fluctuation of the chains. We describe both mechanisms thermodynamically as a microstructural reconfiguration, where the backbone stiffens to motivate solvent (out)flow and accommodate contraction. Via simple steady-state energetic analysis, under the simplest case of isotropic contraction, we quantify the mechanical energy required to achieve contraction as a function of polymer chain density and molecular motor density. We identify two limit cases, (fm) fast MM activation for which MMs provide all the available mechanical energy instantaneously and leave the polymer in a stiffened state, i.e. their activity occurs at a time scale that is much smaller than solvent diffusion, and (sm) slow MM activation for which the MM activation timescale is much longer. To achieve the same final contracted state, fm requires the largest amount of work per unit reference volume, while sm requires the least. For all intermediate cases where the timescale of MM activation is comparable with that of solvent flow, the required work ranges between the two cases. We provide all these quantities as a function of chain density and MM density. Finally, we compare our results with experiments and observe good agreement

Homogenization of heterogeneous Cauchy-elastic materials leads to Mindlin second-gradient elasticity

Through a second-order homogenization procedure, the explicit relation is obtained between the non-local parameters of a second gradient elastic ma- terial and the microstructure of a composite material. This result is instru- mental for the definition of higher-order models, to be used for the analysis of mechanics at micro- and nano-scale, where size-effects become important. The obtained relation is valid for both plane and three-dimensional prob- lems and generalizes earlier findings by Bigoni and Drugan (Analytical deriva- tion of Cosserat moduli via homogenization of heterogeneous elastic materials. J. Appl. Mech., 2007, 74, 741753) from several points of view: i) the result holds for anisotropic phases with spherical or circular ellipsoid of inertia; ii) the displacement boundary conditions considered in the homogenization procedure is independent of the characteristics of the material; iii) a perfect energy match is found between heterogeneous and equivalent materials (instead of an optimal bound). From the obtained solution it follows that the equivalent second-gradient Mindlin elastic solid: a) is positive definite only when the discrepancy tensor is negative defined; b) the non-local material symmetries are the same of the discrepancy tensor; c) the non-local effective behaviour is affected by the shape of the RVE, which does not influence the first-order homogenized response. Finally, explicit derivations of non-local parameters from heterogeneous Cauchy elastic composites are obtained in particular cases